Atomistic vs. Coarse Grained Simulations

Atomistic vs. Coarse Grained Simulations

all atoms vs. four-to-one mappinglong range vs. short range interactions only quantitative vs. semi-quantitative slow (ns) vs. fast (ms)

1 coarse grained water

4 atomistic water

atomistic coarse grained

composition:1600 DPPC250000 H2O

15 ns 50 ns 100 ns

180 ns 250 ns150 ns

1 ns 5 ns0 ns

cell size: 20x20x20 nm

simulation time:250 ns

Aggregation into a DPPC bilayer – coarse grained model

starting structure (t=0 ns)

Surrounding water

Aggregation of DPPC into vesiclescomposition:1600 DPPC1000000 H2O

cell size: 30x30x30 nm

simulation time:100 ns

0 ns random 5 ns worms 10 ns bicelle

60 ns cup20 ns bicelle 80 ns vesicle

LAMELLAR

STALK

HEMIFUSION

FUSION PORERHOMBIC

CUBIC HEXAGONAL

Lamellar to Hexagonal Transition for DOPE at low hydrationin agreement with experiment (Rand etal)

t = 0ns t = 20 ns t = 100 nsT=280 -> 320K stalk formation hexagonal phase

t = 20 ns t = 100 ns stalk formation hexagonal phase

Folding Transition States in Proteins

In collaboration with the group of Chris Dobson in Cambridge we have looked at transition states in the folding of SH3 domains.

Objective: To evaluate the folding propensity of proposed transition states (TS) of the a-spectrin

SH3 domain using molecular dynamics (MD) simulations with an explicit representation of the solvent.

Some of the proposed transition states fold other do not.

InitNative

run 1

Configuration 3Configuration 4

run 2

Configuration 2

Examples showing the native state, a proposed transition state and results of 2 independent folding simulations.

Foldingsuccessful

Foldingunsuccessful

Status of our contribution:

1. Trajectories of the simulations mentioned above can be made available on request2. While we have not appointed anyone specifically on the project we are in the

process of advertising.3. Our aim is to specifically appoint a person focusing on code development who could interact with those groups involved in methods development and exploit

our preexisting simulations..